4. Abnormal uterine bleeding (AUB)
One of the most common
health concerns of women
can present in many ways, from
infrequent episodes
(oligomenorrhea) to excessive
flow (heavy menstrual bleeding,
or prolonged duration of
menses and intermenstrual
bleeding)
This lecture will focus only on
heavy menstrual bleeding
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
5. Review: Normal Menstrual blood flow
mean duration of the
menstrual cycle is 28 ± 7
days.
Average menstrual blood
loss (MBL) is 35 mL.
(normal value: 10-80ml)
Average number of days
of menses: 4 days (normal
range: 2-7 days)
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
6. Abnormal uterine bleeding (AUB)
Bleeding is abnormal/heavy
if:
it occurs at intervals of 21
days or less, or 35 days or
more;
Lasts longer than 7 days;
MBL of 80 mL or greater
the term dysfunctional
uterine bleeding (DUB) is no
longer favored and should be
discarded.
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
7. PALM-COIEN classification of AUB
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
8. Diagnosis Nomenclature:
the acronym AUB is followed by the letters PALM-COEIN and
a subscript 0 or 1 associated with each letter to indicate the
absence or presence, respectively, of the abnormality.
Example #1: A patient with abnormal bleeding due to a polyp
:
AUB-P1A0L0M0-C0O0E0I0N0
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
9. Diagnosis Nomenclature:
Example #2: A patient with abnormal bleeding that is both
irregular and heavy may have endometrial hyperplasia due to
anovulation.
AUB- P0A0L0M1- C0O1E0I0N0
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
10. ENDOMETRIAL POLYPS (AUB-P)
localized overgrowths of endometrial
tissue, containing glands, stroma, and
blood vessels, covered with epithelium.
Most commonly found in reproductive-age
women
estrogen stimulation is thought to play a
key role in their development.
Usually benign.
Women with symptomatic polyps can be
treated safely and effectively with operative
hysteroscopy
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
11. ADENOMYOSIS (AUB-A)
presence of endometrial glands and stroma in the
uterine myometrium. ectopic endometrial tissue
leads to hypertrophy of the surrounding
myometrium.
Risk factors: Multiparity (most significant) and any
process that allows for penetration of endometrial
glands and stroma past the basalis layer (e.g.,
dilation and curettage, cesarean delivery,
spontaneous abortion)
Enlarged, asymmetric uterus on ultrasound
Abnormal bleeding due to adenomyosis is thought
to be a result of altered uterine contractility and is
associated with profound dysmenorrhea.
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
12. LEIOMYOMA (AUB-L)
Also called fibroids, are benign tumors of the uterine
myometrium.
pathogenesis : myometrial injury leading to cellular
proliferation, decreased apoptosis, increased production of
extracellular matrix, and overexpression of transforming growth
factor beta that leads to fibrosis of these tumors.
Mechanisms by which fibroids cause abnormal bleeding are
varied and depend on size, location, and number:
Intracavitary/submucous fibroids
intramural fibroids
Subserous fibroids
Management:
Medical management
Surgical : hysterectomy, myomectomy
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
13. MALIGNANCY (AUB-M)
vulvar, vaginal, cervical, endometrial, uterine, and adnexal (ovarian or
fallopian tube) cancers.
Bleeding from cervical malignancy classically presents as coital bleeding
or intermenstrual bleeding
mostly secondary to prolonged exposure to hyperestrogenic state
(chronic anovulation, PCOS, obesity, nulligravidity, etc)
Lynch syndrome, or hereditary nonpolyposis colorectal cancer, is an
autosomal dominant disease caused by a disruption in the mismatch
repair (MMR) genes carries a 40% to 50% lifetime risk of endometrial
cancer (mostly before the age of 45.)
estrogen-producing ovarian tumors (ex. Granulosa theca cell tumors)
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
14. COAGULOPATHY (AUB-C)
disorders of blood coagulation such as von Willebrand disease
(most common), prothrombin deficiency, hemophilia, leukemia,
severe sepsis, idiopathic thrombocytopenic purpura, and
hypersplenism
Routine screening mainly indicated for the adolescent who has
prolonged heavy menses beginning at menarche.
In adults, screening for these disorders indicated by clinical signs
such as bleeding gums, epistaxis, or ecchymosis.
Other disorders that produce platelet deficiency, such as Chronic
anticoagulation as a result of heparin, low-molecular-weight
heparin, direct thrombin inhibitors, and direct factor Xa inhibitors
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
15. CH ristocetin cofactor should be obtained to rule out a coagula-
Adults with HMB and h/o either
One of the following Two of the following
Testing
Figure 26.6 Diagnostic approach to adults with abnormal uterine
bleeding due to coagulopathy. (Data from Kouides PA, Conard J,
Peyvandi F, et al. Hemostasis and menstruation: appropriate investi -
gation for underlying disorders of hemostasis in women with exces -
sive menstrual bleeding. Fertil Steril. 2005;84[5]:1345-1351.)
100 1000
al blood loss (mL)
5
ratio of endogenous concentra -
prostaglandin E and menstrual
endometrium; persistent endo -
H, Kelly RW, et al. The synthesis
roliferative endometrium. JClin
289.)
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
16. OVULATORY DYSFUNCTION (AUB-O)
the predominant cause of ovulatory
dysfunction postmenarchal and
premenopausal women is secondary to
alterations in neuroendocrine function.
there is continuous estradiol production
without corpus luteum formation and
progesterone production continuously
proliferating endometrium, which may
outgrow its blood supply necrosis.
uniform slough to the basalis layer does not
occur, which produces excessive uterine
bleeding.
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
17. OVULATORY DYSFUNCTION (AUB-O)
Anovulatory bleeding occurs most commonly during the
extremes of reproductive life: in the first few years after
menarche and during perimenopause.
In the adolescent: anovulation is due to an immaturity of the
hypothalamic-pituitary- ovarian (HPO) axis and failure of
positive feedback of estradiol to cause a luteinizing hormone
(LH) surge.
In the perimenopausal woman: lack of synchronization
between the components of the HPO axis occurs as the
woman approaches ovarian decline at menopause.
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
18. OVULATORY DYSFUNCTION (AUB-O)
the patterns of anovulatory bleeding may be
oligomenorrhea, intermenstrual bleeding, or heavy
menstrual bleeding.
What are the causes of anovulation?
1. extremes of reproductive life
2. polycystic ovary syndrome (PCOS)
3. hypothalamic dysfunction (related to weight loss, severe
exercise, stress, or drug use
4. abnormalities of other nonreproductive hormone (thyroid
hormone, prolactin, and cortisol)
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
19. IATROGENIC(AUB-I)
abnormal bleeding resulting from medications
most common of these are hormonal preparations, including selective
estrogen receptor modulators, and gonadotropic releasing hormone
agonists and antagonists.
Hyperprolactinemia can result from central nervous system dopamine
antagonism of certain antipsychotic drugs (eg risperidone)
combined and progesterone-only oral contraceptives may result in
breakthrough bleeding (BTB).
interactions between oral contraceptives and other medications, such as
antibiotics and anticonvulsants may alter circulating levels of steroids,
allowing follicular recruitment and increased endogenous levels of estro-
gen.
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
20. ENDOMETRIAL (AUB-E)
heavy menstrual bleeding in the absence of
other abnormalities are thought to have
underlying disorders of the endometrium or
are otherwise unclassified.
In the past, this category has been called
“ovulatory dysfunctional uterine bleeding.”
the primary line of defense to excessive
bleeding during normal menses is the
formation of the platelet plug, followed by
uterine contractility, largely mediated by
prostaglandin F2α (PGF2α).
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
21. ENDOMETRIAL (AUB-E)
thus prolonged and heavy bleeding can occur
with abnormalities of the platelet plug or
inadequate uterine levels of PGF2α.
In some women with heavy menstrual
bleeding, there is excessive uterine production
of prostacyclin, a vasodilatory prostaglandin
that opposes platelet adhesion and may also
interfere with uterine contractility.
Deficiency of uterine PGF2α or excessive
production of PGE (vasodilatory prostaglandin)
may also explain ovulatory DUB
Low PGF2α/PGE increase menstrual blood
loss
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
22. NOT OTHERWISE SPECIFIED (AUB-N)
Abnormal bleeding not classified in the previous categories
is considered AUB-N.
Examples of such conditions may include foreign bodies or
trauma. Treatment is tailored to the specific cause.
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
24. 1. Medical History
Menstrual history: frequency, duration, and amount of bleeding
inquire whether and when the menstrual pattern changed.
Describe the menstrual abnormality as oligomenorrhea,
polymenorrhea, heavy menstrual bleeding, or intermenstrual
bleeding.
Menstrual calendar to record her bleeding episodes helpful way
to characterize definitively the bleeding episodes.
Symptoms present for the majority of the preceding 6 months are
considered chronic
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
25. The menstrual history
For all patients:
• Age at menarche
• Cycle length
• Duration of bleeding
• Perception of flow: heavy, medium or light
• Menstrual product use
• First day of LMP
• Dysmenorrhea
Holland-Hall C. Heavy menstrual bleeding in adolescents:Normal variant or a bleeding disorder.http://contemporaryobgyn.modernmedicine.com/
27. The menstrual history
For patients reporting heavy menstrual bleeding:
• Lasts more than 7 days
• Soaking through pads/tampons in 1h for 2-3h in a row
• Require frequent pad or tampon changes (soaking
more than one every 1-2 hour.
• Passing blood clots > 1 inch in diameter (“about the
size of a quarter”)
Holland-Hall C. Heavy
menstrual bleeding in
adolescents:Normal
variant or a bleeding
disorder.http://contempor
aryobgyn.modernmedicin
e.com/
Menstruation in girls and
adolescents: using the
menstrual cycle as a vital
sign. Committee Opinion
No. 651. American
College of Obstetricians
and Gynecologists.
Obstet Gynecol
2015;126:e143–6
28. The menstrual history
For patients reporting heavy menstrual bleeding:
• Using “double protection” (pad plus tampon or 2 pads
together)
• Flooding or gushing sensation
• Frequent “accidents” or leaking through protection
• Hemorrhage from a corpus luteum
• Diagnosed with anemia
• Associated with history of excessive bruising or
bleeding or a family history of bleeding disorder
Holland-Hall C. Heavy
menstrual bleeding in
adolescents:Normal variant
or a bleeding
disorder.http://contempora
ryobgyn.modernmedicine.c
om/
Menstruation in girls and
adolescents: using the
menstrual cycle as a vital
sign. Committee Opinion
No. 651. American
College of Obstetricians
and Gynecologists.
Obstet Gynecol
2015;126:e143–6
29. MEDICAL history
For patients reporting personal history of >1 of the
following symptoms:
• Epistaxis (>10min, or requiring medical attention),
spontaneous bruising (>2cm), or minor wound
bleeding (>5min)
• Bleeding from oral cavity or GI tract without an
obvious anatomic lesion
• Prolonged or excessive bleeding after dental
extraction or surgery
• Hemorrhage that required transfusion
Menstruation in girls and
adolescents: using the
menstrual cycle as a vital
sign. Committee Opinion
No. 651. American
College of Obstetricians
and Gynecologists.
Obstet Gynecol
2015;126:e143–6
Holland-Hall C. Heavy
menstrual bleeding in
adolescents:Normal variant
or a bleeding
disorder.http://contempora
ryobgyn.modernmedicine.c
om/
30. MEDICAL history
Social history –social stressors, substance use, and
exercise patterns, and athletic competition.
Family history –bleeding disorders, menstrual
disorders, diabetes and thyroid
Past medical history – systemic illness, including
hematologic or renal disease, and current or recent
medications
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
31. MEDICAL history
Sexual history
contraception and condom use
number of partners
history of sexually transmitted infections or
current symptoms (eg, vaginal discharge, pelvic
pain);
previous pregnancy or abortion
history of sexual abuse or assault
De Silva N. Abnormal uterine bleeding in adolescents: Evaluation and approach to diagnosis. August 2016. www.uptodate.com
32. Physical Exam
Vital signs
tachycardia and hypotension
may signal acute hemodynamic
instability and the need for
rapid intervention
The presence of tachycardia,
pallor, or a heart murmur
suggests anemia
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
33. Physical Exam
Petechiae or excessive bruising:
may suggest a platelet defect or
another bleeding disorder.
Obesity, acne, hirsutism, and
acanthosis nigricans : may be
present in a patient with PCOS.
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
Rydz N and Jamieson MA. Managing heavy menstrual bleeding in adolescents. 2013. http://contemporaryobgyn.modernmedicine.com/
34. Palpation of the thyroid gland for enlargement
or other abnormalities.
Examination of the optic fundi and visual field
testing (pituitary tumor)
Sexual maturity rating of the breasts and
assessment for galactorrhea.
Palpation of the abdomen (pregnancy,
uterine/ovarian mass).
Physical Exam
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
Rydz N and Jamieson MA. Managing heavy menstrual bleeding in adolescents. 2013. http://contemporaryobgyn.modernmedicine.com/
35. Physical Exam
External inspection of the
genitalia is sufficient for
diagnosis in most patients.
A sexually active patient may
warrant a complete pelvic
examination (speculum and
bimanual exams).
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
Rydz N and Jamieson MA. Managing heavy menstrual bleeding in adolescents. 2013. http://contemporaryobgyn.modernmedicine.com/
36. Laboratory evaluation
Pregnancy test
Complete blood count including
differential and platelet count;
blood typing
Measure of iron stores
prothrombin time and activated
partial thromboplastin time
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
37. Laboratory evaluation
von Willebrand studies (factor VIII, von
Willebrand factor antigen (VWF:Ag),
and ristocetin cofactor (VWF:RCo)
activities.)
TSH
Test for Chlamydia trachomatis and
Neisseria gonorrhea
pelvic ultrasound
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
38. Laboratory evaluation
Patients with a history of
amenorrhea or irregular bleeding
prior to the onset of heavy
bleeding should have:
FSH and LH
total and free testosterone
levels
Dehydroepiandrosterone
prolactin level
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
40. Management
The management of AUB depends on:
assessment of whether or not the
patient is hemodynamically stable
determination of the underlying cause
medical management based on
etiology and the severity of anemia.
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
41. Establish and/or maintain hemodynamic
stability
Correct acute or chronic anemia
Return to a pattern of normal menstrual cycles
Prevent of recurrence
Prevent long-term consequences of
anovulation (eg, anemia, infertility, endometrial
cancer)
The goals of treatment are to:
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
42. Medical treatment
The goal of medical therapy is to stabilize the
endometrium with estrogen that will provide initial
hemostasis, followed by progestins for endometrial
stability.
Typically, this is achieved with combined oral
contraceptive pills (OCPs) taken continuously for
several months until hemodynamically stable, as
withdrawal of either hormone will cause recurrent
bleeding.
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
43. Episodes of moderate-to-severe
bleeding can typically be treated
effectively with frequent dosing of
combined oral contraceptive pills.
Bennet AR and Gray SH. What to do when she’s bleeding through: the recognition, evaluation, and
management of abnormal uterine bleeding in adolescents. Curr Opin Pediatr 2014, 26:413–419
Medical treatment
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
44. Treatment
In the absence of an organic cause for excessive uterine
bleeding, it is preferable to use medical instead of surgical
treatment, especially if the woman desires to retain her
uterus for future childbearing or will be undergoing natural
menopause within a short time.
the type of treatment depends on whether it is used to stop
an acute heavy bleeding (acute AUB) episode or is given to
reduce the amount of MBL in subsequent menstrual cycles
(Chronic AUB)
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
45. A definitive diagnosis is required before instituting
long-term treatment, and should be made on the
basis of hysteroscopy, sonohysterography, or
directed endometrial biopsies
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
46. ABNORMAL UTERINE BLEEDING: OVULATORY
DYSFUNCTION
A. Adolescents:
after ruling out coagulation disorders, the main direction of
therapy is to temporize because once the HPO axis matures,
the problem will be corrected.
cyclic progestogen (medroxyprogesterone acetate, 10 mg
for 10 days each month for a few months) to produce
reliable and controlled menstrual cycles.
oral contraceptive (OC)may be an option if the problem
persist beyond 6 months.
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
47. ABNORMAL UTERINE BLEEDING: OVULATORY
DYSFUNCTION
B. Perimenopausal woman:
low-dose (20-μg) combined oral contraceptives( in a
nonsmoking woman).
Cyclic Progestogens
C. Reproductive-aged women:
chronic anovulatory bleeding is primarily caused by
hypothalamic dysfunction or PCOS.
Combined oral contraceptives
cyclic progestogens
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
48. ABNORMAL UTERINE BLEEDING:
ENDOMETRIAL
For women with heavy menstrual bleeding, for whom there
is no known cause and anatomic lesions have been ruled
out, the aim of therapy is to reduce the amount of excessive
bleeding.
some women with AUB-E have abnormal prostaglandin
production and some have alterations of endometrial blood
ow.
Options for treatment to reduce blood loss include:
prolonged regimen of progestogens (3 weeks each month);
Oral contraceptive pills will reduce the blood loss by at least 35% in
women with AUB
levonorgestrel intrauterine system (LNG-IUS)
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
49. NONSTEROIDAL ANTI-INFLAMMATORY
DRUGS
prostaglandin synthetase inhibitors that inhibit the biosynthesis of the
cyclic endoperoxides, which convert arachidonic acid to prostaglandins.
block the action of prostaglandins by interfering directly at their receptor
sites..
All NSAIDs are cyclooxygenase inhibitors and thus block the formation of
both thromboxane and the prostacyclin pathway. Nevertheless, NSAIDs
have been shown to reduce MBL, primarily in women who ovulate.
Examples:
mefenamic acid (500 mg, three times daily)
ibuprofen (400 mg, three times daily),
naproxen sodium (275 mg, every 6 hours
after a loading dose of 550 mg)
Given in the first 3 days of
menses or whole duration of
bleeding
Ryntz T, Lobo R.
Chapter 26.
Abnormal Uterine
Bleeding;
In
Comprehensive
Gynecology 7th
edition,
2017;Lobo RA,
Gershenson DM,
Lentz GM, Valea
FA editors; pp
621-633.
50. Anti-fibrinolytic Agents
ε-Aminocaproic acid (EACA), tranexamic acid
(AMCA), and para-aminomethyl benzoic acid
(PAMBA) are potent inhibitors of fibrinolysis
their use is somewhat limited by side effects
mainly GI side effects and can be minimized by reducing the dose
and limiting therapy to the first 3 to 5 days of bleeding.
Due to the increased risks of thrombosis and myocardial infarction,
antifibrinolytic agents should not be combined with oral
contraceptives. Combined treatment with tranexamic acid and the
oral contraceptive pill has been implicated in coronary ulcerated
plaque and acute myocardial infarction
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
51. Gonadotropin-Releasing Hormone Agonists
GnRH agonists may be used to inhibit ovarian steroid
production, as estrogen production is necessary for
endometrial proliferation.
Because of the expense and menopausal side effects of
these agents, their use is limited to women with severe MBL
who fail to respond to other methods of medical
management and wish to retain their childbearing capacity.
More commonly, GnRH agonists are an effective means of
bridging patients to surgical treatment, allowing for
correction of anemia.
Use of an estrogen or progestogen (add-back therapy)
together with the agonist will help prevent bone loss.
Ryntz T, Lobo R.
Chapter 26.
Abnormal Uterine
Bleeding;
In
Comprehensive
Gynecology 7th
edition,
2017;Lobo RA,
Gershenson DM,
Lentz GM, Valea
FA editors; pp
621-633.
53. Acute AUB
In women who are bleeding heavily and are hemodynamically
unstable, the quickest way to stop acute bleeding is with
curettage.
Curettage should also be the preferred approach for older
women and those with medical risk factors for whom high-
dose hormonal therapy may pose a great risk.
May also be managed medically (pharmacologic agents)…
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
54. PHARMACOLOGIC AGENTS FOR ACUTE
BLEEDING
To stop acute bleeding that does not require curettage, the
most effective regimen involves high-dose estrogen.
High-dose estrogen is aimed at stopping acute bleeding,
and is merely a temporary measure.
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
55. Estrogens
estrogen in pharmacologic doses causes rapid growth of the
endometrium.
a rapid growth of endometrial tissue occurs over the
denuded and raw epithelial surfaces
large doses of estrogen may alter platelet activity, thus
promoting platelet adhesiveness.
1. oral conjugated equine estrogen (CEE) 10 mg/day, in four divided doses
2. IV conjugated estrogen: 25 mg q4-6h until the bleeding stops. (No more
than six doses should be administered)
3. combination oral contraceptive (both estrogen and progestin). Four tablets
of an oral contraceptive containing 30 to 35 μg of estrogen taken every 24
hours in divided doses.
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
56. Progestogens
For patients with contraindication to estrogen (e.g., those with prior
thrombosis, certain rheumatologic diseases, estrogen-responsive cancer).
Progestogens not only stop endometrial growth but also support and
organize the endometrium so that an organized slough occurs after their
withdrawal.
With progestogen treatment, an organized slough to the basalis layer
allows a rapid cessation of bleeding.
progestogens stimulate arachidonic acid formation in the endometrium,
increasing the PGF2 /PGE ratio.
medroxyprogesterone acetate (MPA) at a dose of 60 mg daily (20 mg
three times daily) for 7 days followed by 20 mg per day for 3 weeks
Depo-MPA 150 mg intramuscularly followed by oral MPA 60 mg (20 mg
three times daily) for 3 days
norethindrone acetate (30 mg per day)
Ryntz T, Lobo R.
Chapter 26.
Abnormal Uterine
Bleeding;
In Comprehensive
Gynecology 7th
edition, 2017;Lobo
RA,
Gershenson DM,
Lentz GM, Valea FA
editors; pp 621-633.
57. ANDROGENS
Danazol is a synthetic androgen used in doses of 200 mg
daily for the treatment of heavy menstrual bleeding
Limited use because of the side effects of weight gain and
skin problems
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
58. Indications for hospitalization
Hemodynamic instability (eg, tachycardia, hypotension)
Hemoglobin concentration <7 g/dL or <10 g/dL with active
heavy bleeding
Symptomatic anemia (eg, fatigue, lethargy)
Need for intravenous conjugated estrogen (eg, cannot take
oral medications, continued heavy bleeding after 24 hours of
estrogen-progestin combination therapy)
Need for surgical intervention (rare)
De Silva N. Abnormal uterine bleeding in adolescents: Management. March 2017. www.uptodate.com
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
60. 1. Dilatation and curettage (D&C)
Both diagnostic and is therapeutic for the immediate
management of severe bleeding.
For women with markedly excessive uterine bleeding who
may be hypovolemic, a D&C is the quickest way to stop
acute bleeding treatment of choice in hypovolemic
women
D&C may be preferred as an approach to stop an acute
bleeding episode in women older than 35 when the
incidence of pathologic findings increases.
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
61. 1. Dilatation and curettage (D&C)
D&C is only indicated for women with acute bleeding
resulting in hypovolemia and for older women who are at
higher risk of having endometrial neoplasia.
All other women, after having an endometrial biopsy,
sonohysterography, or diagnostic hysteroscopy to rule out
organic disease, are best treated with medical therapy,
without D&C.
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
62. 2. Endometrial Ablation
if medical therapy is not effective or is contraindicated.
Exceptions are women who have very large uteri caused by
fibroids or abnormal pathology, such as endometrial
hyperplasia or cancer.
Alternative to hysterectomy
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
63. 3. Hysterectomy
Surgical removal of the uterus.
reserved for the woman with other indications for
hysterectomy, such as leiomyoma or uterine prolapse.
Usually offered to women with completed family size (no
longer desirous of pregnancy)
used to treat persistent abnormal uterine bleeding after all
medical therapy has failed, or medical therapy is
contraindicated.
Ryntz T, Lobo R. Chapter 26. Abnormal Uterine Bleeding;
In Comprehensive Gynecology 7th edition, 2017;Lobo RA,
Gershenson DM, Lentz GM, Valea FA editors; pp 621-633.
64. Chronic AUB
Multiple treatment options are available for long-
term treatment of chronic AUB:
levonorgestrel intrauterine system
OCs (monthly or extended cycles)
progestin therapy (oral or intramuscular)
tranexamic acid
NSAIDs
De Silva N. Abnormal uterine bleeding in adolescents: Management. March 2017. www.uptodate.com
Hinweis der Redaktion
Abnormal uterine bleeding (AUB) is one of the most common health concerns of women. It can present in many ways, from infrequent episodes, to excessive flow, or prolonged duration of menses and intermenstrual bleeding. Excessive or prolonged bleeding will be discussed in this lecture. We will discuss oligomenorrhea and amenorrhea in a different lecture.
To define excessive abnormal uterine bleeding, it is necessary to de ne normal menstrual ow. e mean interval between menses is 28 days (±7 days). us if bleeding occurs at intervals of 21 days or less or 35 days or more it is abnormal. e mean duration of menstrual ow is 4 days. Few women with normal menses bleed more than 7 days, so bleeding for longer than 7 days is considered to be abnormally prolonged. It is useful to document the duration and frequency of menstrual ow with the use of menstrual diary cards; however, it is di cult to determine the amount of men- strual blood loss (MBL) by subjective means. Several studies have shown that there is poor correlation between subjective judgment and objective measurement of MBL
Abnormal uterine bleeding (AUB) is one of the most common health concerns of women. It can present in many ways, from infrequent episodes, to excessive flow, or prolonged duration of menses and intermenstrual bleeding. Excessive or prolonged bleeding will be discussed in this lecture. We will discuss oligomenorrhea and amenorrhea in a different lecture.
e etiologies that constitute the rst group (PALM) are struc- tural or histologic causes that are diagnosed through imaging or biopsy. ose that compose the second group (COEIN) are nonstructural
Although it may seem that these patients could be considered as having iatrogenic abnormal bleeding due to prescribed medications,the heavy bleeding is a result of a derangement in the coagulation cascade and is thus categorized here.
BTB most likely reflects alterations in the structural integrity, vascular density, and vascular morphology of the endometrial vasculature due to alterations in the expression of steroid receptors and the integrity of the endometrial epithelial layer (Smith, 2005).
The patient’s menstrual history can help focus the differential diagnosis. The patient should be asked about onset of menarche, cycle length and variabil- ity over time, and amount of menstrual blood loss. Patients may use the term ‘heavy’ to describe periods that are actually painful, long, or occur at frequent intervals; therefore, clarification is important. Many patients now keep track of their menses using a smartphone application, which can be helpful to review. A history of heavy menstrual flow during the first period is suggestive of a bleeding disorder such as von Willebrand disease. Regular cyclic menses with voluminous flow may also indicate an under- lying bleeding disorder. Regular cycles with premen- strual symptoms, such as breast discomfort, cramps, and bloating prior to each menses, are suggestive of ovulatory cycles, whereas anovulatory cycles are usually irregular and can imply an underlying endo- crinopathy such as PCOS or thyroid disease. Inter- menstrual bleeding is concerning for an anatomic cause such as cervicitis from a sexually transmitted infection or secondary to the concurrent use of hormonal contraception, especially long-acting progestin-only methods. Following a conversation about confidentiality, all adolescents should also be privately asked about history of sexual activity, in- cluding both consensual and coerced sex.
In the absence of a practical means to measure blood loss, the clinician must rely upon indirect indicators of heavy flow, such as passing blood clots larger than 2.5 cm (1 inch) in diameter, the need to change sanitary protection during the night, signs or symptoms of volume depletion during the menstrual period, and measurement of hemoglobin or hematocrit
Sexual history –should be obtained without the caregiver present. History should include information regarding contraception and condom use; number of partners; new partners; history of sexually transmitted infections or current symptoms (eg, vaginal discharge, pelvic pain); previous pregnancy or abortion; whether sexual activity was forced or consensual; and whether the adolescent has a history of sexual abuse or assault
Past medical history –should include information about systemic illness, including hematologic or renal disease, and current or recent medications (including over-the-counter medications and complementary/alternative agents) (table 2) [14]. Aspirin and aspirin-containing over-the-counter medications should be asked about specifically. (See "Approach to the child with bleeding symptoms", section on 'Medication'.)
●Review of systems – The review of systems should include information about weight change (loss or gain), fatigue, self-induced vomiting as a means of weight control, disordered eating behaviors, hirsutism, acne, visual changes, headaches, galactorrhea, change in bowel habits, and abdominal pain (table 2)
Assessment of body type and fat distribution (eg, Cushing syndrome, Turner syndrome).
Palpation of the thyroid gland for enlargement or other abnormalities.
Signs of androgen excess (eg, hirsutism, acne, male-pattern balding) - pcos
Examination of the optic fundi and visual field testing to evaluate the possibility of a pituitary tumor.
Sexual maturity rating of the breasts and assessment for galactorrhea. Breast development provides evidence of estrogenization.
••Palpation of the abdomen (pregnancy, uterine mass, ovarian mass).
A sexually active patient may warrant a complete pelvic examination (speculum and bimanual exams), particularly if pain is present, if her heavy bleeding represents an acute change from her previous pattern, or if she fails to respond as anticipated to treatment.
A speculum examination is not always indicated, especially when the teen is precoital and the bleeding is unlikely to be from the lower genital tract. If a more complete examination is indicated in a young teenager or “tween,” vaginoscopy is a valuable tool and less traumatic than a speculum exam.
If a pelvic exam is absolutely needed in cases of massive bleeding, trauma, or suspected congenital anomolies, one can be performed under anesthesia.
Patients requiring hospitalization or blood trans- fusion or who present with a hemoglobin level of less than 10g/dl have a higher (20–30%) likelihood of having an underlying bleeding disorder [2&]. For patients in whom an underlying bleeding disorder is suspected, coagulation studies, including prothrom- bin time/international normalized ratio, activated par- tial thromboplastin time, and fibrinogen and von willebrand panel are indicated
The von Willebrand panel should include von Willebrand fac- tor (vWF) antigen, ristocetin cofactor assay, and factor VIII as an initial screen. If feasible, the von Wil- lebrand panel should be obtained during the first 3 days of menses because the estradiol-masking effects (which inflate vWF levels) are lowest at this time. If a patient is already taking combined hormonal contra- ceptives, a laboratory evaluation can be obtained near the end of the placebo week with the caveat that the results may not reflect true levels. Acquiring a blood type is helpful in interpreting these results because those who have blood type O have lower levels of vWF than those who have type A or B.
If a bleeding disorder is suspected, prothrombin time and activated partial thromboplastin time should be measured. Because these studies will not always be abnormal in patients with mild bleeding disorders, it is reasonable also to obtain von Willebrand studies, including factor VIII, von Willebrand factor antigen (VWF:Ag), and ristocetin cofactor (VWF:RCo) activities. According to guidelines published by the National Heart, Lung, and Blood Institute, VWF:Ag and VWF:RCo levels under 30 IU/dL provide a definitive diagnosis of von Willebrand disease. Levels of 30 IU/dL to 50 IU/dL are considered low and may be seen in patients with partial quantitative VWF deficiency (type 1 disease)
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A screening thyroid-stimulat- ing hormone should also be considered in patients with more than mild bleeding. Clinicians should have a low threshold for obtaining urine nucleic acid amplification tests for Chlamydia trachomatis and Neisseria gonorrheae [8] given the prevalence of sexu- ally transmitted infections in this age group.
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Sexually active adolescents should be tested for pregnancy and STIs, including gonorrhea and chlamydia, which can cause endometritis, cervical friability, and bleeding
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A pelvic ultrasound may be indicated if there is a suspicion of structural pathology (pelvic mass or uterine pathology) or if the patient does not respond to treatment as expected, or if pelvic exam is not possible
If heavy vaginal bleeding is ac- companied by focal abdominal pain or a pelvic mass, a pelvic ultrasound is recommended to assess for mass lesions including ectopic pregnancy, malignancy, or ovarian masses
atients with a history of amenorrhea or irregular bleeding prior to the onset of heavy bleeding should have an FSH, LH, total and free testosterone levels, dehydroepiandros- terone, and, possibly, a prolactin level to screen for PCOS, primary ovarian insufficiency, and hyperpro- lactinemia
The management of AUB begins with an assessment of whether or not the patient is hemodynamically stable, followed by determination of the underlying cause, and then proceeding with medical manage- ment based on etiology and the severity of anemia.
Fortunately, surgical intervention is rarely necessary in adolescents as more than 90% of patients improve with medical management
The management of AUB begins with an assessment of whether or not the patient is hemodynamically stable, followed by determination of the underlying cause, and then proceeding with medical manage- ment based on etiology and the severity of anemia.
Administration of exogenous estrogen permits additional endometrial proliferation, which heals the sites of endometrial bleeding, and provides hemostasis [2,7]. Administration of progestin stabilizes the endometrial lining
Clinicians may be concerned that the high doses of estrogen that are sometimes necessary to control severe abnormal uterine bleeding may cause premature closure of the growth plates, reducing ultimate adult height. However, by the time of menarche, most female adolescents have already undergone their growth spurt (figure 1) and achieved approximately ≥95 percent of adult height.
Fortunately, surgical intervention is rarely necessary in adolescents as more than 90% of patients improve with medical management
To decrease bleeding of the endometrium, it would be ideal to block selectively the synthesis of prostacyclin alone, without decreasing thromboxane formation, because the latter increases platelet aggregation Presently, there are no NSAIDs that possess this ability
ndications for hospitalization — Indications for hospitalization include [2,9,19]:
●Hemodynamic instability (eg, tachycardia, hypotension, orthostatic vital signs)
The need for blood transfusion is assessed on a case-by-case basis, depending upon the hemoglobin, blood loss, orthostatic vital signs, and the ability to rapidly gain control of hemodynamic stability and bleeding through prompt administration of intravenous (IV) fluid, plasma expanders, and hormonal therapy [2,3]. (See "Approach to vaginal bleeding in the emergency department", section on 'Determine hemodynamic status'.)
●Hemoglobin concentration <7 g/dL or <10 g/dL with active heavy bleeding
Home management with daily monitoring may be possible for patients with hemoglobin between 8 and 10 g/dL if the patient is hemodynamically stable and the patient and family are reliable and can maintain close telephone contact.
●Symptomatic anemia (eg, fatigue, lethargy)
●Need for intravenous conjugated estrogen (eg, cannot take oral medications, continued heavy bleeding after 24 hours of estrogen-progestin combination therapy) or surgical intervention (see 'Intravenous estrogen' below and 'Combination therapy' below)
●Need for surgical intervention (see 'Refractory uterine bleeding' below)
Endometrial resection is usually carried out with a loop electrode, roller ball, or grooved or spiked electrode to vapor- ize the endometrium. Hysteroscopic surgical techniques have the advantage of dealing de nitively with associated pathology (e.g., polyps, submucous broids), although they require greater surgical skill, have longer procedure times, and have higher com- plication rates compared with nonresectoscopic methods.
Endometrial resection is usually carried out with a loop electrode, roller ball, or grooved or spiked electrode to vapor- ize the endometrium. Hysteroscopic surgical techniques have the advantage of dealing de nitively with associated pathology (e.g., polyps, submucous broids), although they require greater surgical skill, have longer procedure times, and have higher com- plication rates compared with nonresectoscopic methods.
Once the acute episode of bleeding has been con- trolled, multiple treatment options are available for long-term treatment of chronic AUB. Management after the acute episode of bleeding is controlled and the initial course of hormonal therapy is complete depends upon the initial hormonal regimen, the patient's desire for contraception, and whether or not she remains anemic.
Effective medical therapies include the levonorgestrel intrauterine system, OCs (monthly or extended cycles), progestin therapy (oral or intramuscular), tranexamic acid, and nonsteroidal anti- inflammatory drugs (6). If a patient is receiving IV con- jugated equine estrogen, the health care provider should add progestin or transition to OCs. Unopposed estrogen should not be used as long-term treatment for chronic AUB.